Patients with uncontrolled epilepsy may have impairment of language and memory associated with their seizures. In addition, it is critical to map these functions when surgery is being considered. We are using imaging methods in an effort to replace more invasive approaches to detecting the effects of epilepsy on language and memory, and for preoperative mapping. Methods: We use positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to map language and memory in patients with temporal lobe epilepsy to perform non-invasive evaluation of functional cortex, and study the effect of epilepsy on cognitive anatomy in children and adults with seizures. Our studies in both normal volunteers and patients with uncontrolled seizures have shown that imaging evaluation compares well with more invasive procdures such as electrostimulation mapping and the intracarotid sodium amytal test. We also evaluate the effect of seizures on the development of functional cognitive anatomy. Recent findings: 10 normal children were studied on a 1.5 T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation, letters. Studies were analyzed with a cross correlation algorithm. A region of interest analysis was used to determine extent and magnitude, and laterality of brain activation. Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca?s area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% more activation than adults, with a trend for greater degree of activation AR. The degree of laterality appeared less in children than for adults in IFG and MFG but this was not significant. CONCLUSIONS: In a test of verbal fluency children tended to activate cortex more widely than adults but activation patterns for fluency appear to be established by middle childhood. Such tests may be applied to pediatric patient populations for determining language dominance. The greater activation found in children may reflect developmental plasticity for the ongoing organization of neural networks which underlie language capacity. fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. We identified temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 agreement between visual and ROI reading with IAT was 0.71 to 0.77. Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. Conclusions: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis. The extent to which visual word perception engages speech codes (i.e., phonological recoding) remains a crucial question in understanding mechanisms of reading. In this study, we used functional magnetic resonance imaging (fMRI) techniques combined with behavioral response measures to examine neural responses to focused versus incidental phonological and semantic processing of written words. Three groups of subjects made simple button-pressing responses in either phonologically (rhyming-judgment) or semantically (category-judgment) focused tasks or both tasks with identical sets of visual stimuli. In the phonological tasks, subjects were given both words and pseudowords separated in different scan runs. The baseline task required feature search of scrambled letter strings created from the stimuli for the experimental conditions. The results showed that cortical regions associated with both semantic and phonological processes were strongly activated when the task required active processing of word meaning. However, when subjects were actively processing the speech sounds of the same set of written words, brain areas typically engaged in semantic processing became silent. In addition, subjects performed both the rhyming- and semantic tasks showed diverse and significant bilateral activation in the prefrontal, temporal, and other brain regions. Taken together, the pattern of brain activity provides evidence of a neural basis supporting the theory that in normal word reading, phonological recoding is automatic and facilitates semantic processing of written words, while rapid comprehension of word meaning requires devoted attention. These results also raise questions about including multiple cognitive tasks in the same neuroimaging sessions. Current Studies: we are developing new paradigms, particularly using event-related strategies, appropriate for various age groups and developmental levels (with an emphasis on younger age groups, particularly children younger than 7 years old). These studies will primarily use the 3T magnet. We will also design fMRI activation studies using arterial spin tagging at 3T that will examine developmental differences in cerebral blood flow and BOLD signal response. We also plan to study the effects of temporal lobectomy on the functional anatomy of language and working memory.